tbuckley/cabot-search huggingface dataset:
The safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for patients (pts) with hepatocellular carcinoma (HCC): Updated results of a phase 2 study.
Authors: Yiwen Chen, Yan Shen, Min Zhang, Jian Wu, Shunliang Gao, Risheng Que, Jun Yu, Xiaofeng Tang, Xueli Bai, Tingbo Liang
Journal: Journal of Clinical Oncology (2023)

e16202 Background: Adjuvant therapy may have an important role in decreasing recurrence rates and improve survival in selected pts with HCC following surgical resection. However, there is no standard treatment options or strategies. This study aimed to investigate the safety and efficacy of donafenib combined with anti-PD-1 antibody as adjuvant therapy for HCC pts with high risks of recurrence. Methods: This prospective, open-label, single-arm study planned to enroll 30 pts who had undergone radical surgery and were diagnosed as HCC confirmed by histology or cytology with any of the following risk factors: a) Microvascular invasion (MVI); b) Satellite nodules in specimens; c) &gt;3 tumor nodules; d) Portal vein tumor thrombosis (excluded main portal vein invasion). Donafenib combined with anti-PD-1 antibody was initiated at 4 to 8 weeks after surgical resection and continued for up to six months. The primary endpoint was the cumulative 1-year recurrence-free survival rate (RFSR). The secondary endpoints were recurrence-free survival (RFS), overall survival, and safety. Results: As of December 31st, 2022, a total of 23 pts received donafenib plus anti-PD-1 antibody (toripalimab) with a mean follow-up of 7.6 months (safety set). The most common risk factor was MVI (91%). 20 pts were included in efficacy set (three pts were excluded due to ineligibility), of whom 16 pts had one risk factor and four had two. Intrahepatic recurrence occurred in 3 pts (15%) and no extrahepatic metastasis or death was reported. The RFSR at one year was 83.0% (90%CI, 61.6%-93.1%) in all the pts from efficacy set, 81.9% (90%CI, 59.6%-92.6%) and 92.3% (90%CI, 66.0%-98.5%) in pts with MVI and MVI-low risk, and 85.1% (90%CI, 59.6%-95.1%) in pts with only one risk factor. The median RFS was not reached. The incidence of grade 3 adverse events related to donafenib and/or toripalimab was 52.2% (12/23). No pts had grade 4/5 adverse events. Adverse events leading to withdrawal of any and both treatments occurred in six (26.1%) and one (4.3%) pts, respectively. The most common grade 3 treatment-related adverse events (occurred in more than one patient) were palmar-plantar erythrodysesthesia syndrome (17.4%), rash (17.4%), alanine aminotransferase increased (13.0%), and aspartate aminotransferase increased (8.7%). Conclusions: These results were consistent with earlier reports. The combination of donafenib and toripalimab may be a promising adjuvant therapy for pts with MVI, satellite nodules or multiple tumor after hepatectomy. No safety issues were noted. Clinical trial information: NCT04418401 . [Table: see text]
Investigating the association (assoc) between mental health illness (MHI) and development of prostate cancer (PC) in a nationwide matched cohort of &gt;5,000,000 US Veterans.
Authors: Zachary Klaassen, Jessica Janes, Joshua Parrish, Rashid K. Sayyid, Sydney McIntire, Amanda Marie De Hoedt, Raj Satkunasivam, Stephen B. Williams, Christopher J.D. Wallis, Martha K. Terris, Stephen J. Freedland
Journal: Journal of Clinical Oncology (2023)

e17113 Background: Previous reports suggest that men with MHI who subsequently develop PC have worse outcomes. However, it has not been established whether a history of MHI is associated with a PC diagnosis (dx) or more aggressive PC. The objective of this study was to (i) investigate the assoc between MHI and development of PC, and (ii) in a subset of men with available Gleason Score (GS) data, assess the assoc between MHI and aggressive PC as measured by GS ≥7 PC at dx. Methods: This was a retrospective matched-cohort analysis to assess the assoc between MHI and time to PC dx in the Veterans Affairs (VA) Health Care System. Men with an ICD code for MHI dx between 2000-2020 were matched 1:1 to men with no MHI dx in the same time frame. The MHI dx date of the exposed (exp) male was assigned as the index date of the unexp male. Variables matched on included race, age at MHI exp (+/- 3 years), census region, and median household income. Uni- and multivariable competing risks models were used to test the assoc between MHI and time to PC using death from other causes as competing risk. In a subset of men with GS data available, logistic regression was used to test the assoc between MHI and GS ≥7 at PC dx. All multivariable models were adjusted for age, race, census region, income, Charlson Comorbidity Index, year of MHI index, and year of VA entry. Results: There were 2,597,810 MHI-exp men matched 1:1 to unexp men. During a median (Q1, Q3) follow up of 128 (65, 192) months, 390,977 PC diagnoses were observed (172,442 MHI-exp vs. 218,535 unexp). MHI-exp men were significantly less likely to be diagnosed with PC than unexp men in both uni- (HR: 0.798, 95% CI: 0.793-0.803) and multivariable (HR: 0.763, 95% CI: 0.758-0.768) analysis. Cumulative incidence estimates at 3, 5, 10, and 20 years were 2.1%, 3.1%, 5.2%, and 8.5%, respectively, for MHI-exp men vs 2.9%, 4.2%, 6.9%, and 11.7%, respectively, for unexp men. Among men with PC and available GS data (n = 51,404), 32,645 had GS ≥7 PC, of which 20,749 were MHI-exp vs 11,896 unexp. MHI-exp men had significantly higher odds of GS ≥7 PC in both uni- (OR: 2.38, 95% CI: 2.32-2.43) and multivariable (OR: 1.97, 95% CI: 1.92-2.02) analysis. Conclusions: Men with MHI are 20% less likely to be diagnosed with PC, however when diagnosed, are nearly 2 times more likely to have aggressive PC compared to non-MHI men. Although speculative based on the nature of the study, this may be due to poorer access to preventative health services resulting in delayed diagnoses.
Examining molecular testing practices and targeted therapy use in advanced/metastatic non-small cell lung cancer (mNSCLC): A quality improvement initiative across ten community cancer centers.
Authors: Gilberto Lopes, Bethany Delcuze, Ilona Dewald, Kelly E. McKinnon, Jeffrey D. Carter, Cherilyn Heggen
Journal: Journal of Clinical Oncology (2023)

e21191 Background: A growing number of targeted therapy approvals for mNSCLC have dramatically increased requirements for molecular testing. Identifying and addressing real-world challenges mNSCLC care teams face due to resulting workflow shifts is essential to optimize patient outcomes. Methods: In March–September 2022, 126 health care professionals (HCPs) who treat NSCLC at 10 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to biomarker testing and targeted therapy use. HCPs (N = 105) participated in interdisciplinary audit and feedback (AF) sessions to examine clinical evidence and develop clinic-specific action plans to address identified gaps. Results: Participants represented the interprofessional NSCLC care team: medical oncologists (32%), pathologists (1%), radiation oncologists (1%), pulmonologists (2%), PCP/other physicians (5%), advanced practice professionals (22%), nurses (19%), and other HCPs (e.g. patient navigator, practice manager; [19%]). At the time of the program there were 9 NCCN-recommended biomarkers for mNSCLC. Less than half of HCPs reported regular testing for 4 of these biomarkers (Table 1). The majority of HCPs were somewhat (52%) or very/extremely (23%) likely to start treatment prior to receiving molecular testing results. Top reported barriers to integrating molecular diagnostics into routine practice were biopsy tissue availability/quality (45%) and determining whether to begin treatment prior to receipt of molecular testing results (43%). Gap-oriented clinic action plans aimed to improve communication between oncologists, pulmonologists, and pathologists to increase quality and efficiency of testing. A targeted therapy toolkit was developed with a panel of oncology and pathology experts and distributed to participants to address gaps in knowledge of testing practices and guidelines. HCP confidence in biomarker testing increased from 72% to 92% following the intervention. More HCPs correctly answered knowledge (43% pre-AF vs 61% post-AF) and competence (29% pre-AF vs 54% post-AF) questions following participation in the AF sessions. Conclusions: While molecular testing is critical for mNSCLC care, HCPs report sub-optimal rates of conducting testing prior to treatment and incorporating results into treatment planning. Here, we highlight an unmet need for improved interdisciplinary communication and coordination in mNSCLC care teams and an educational intervention strategy that can be used to improve HCP biomarker and targeted therapy use in mNSCLC. [Table: see text]
A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: A randomized, controlled trial with two-staged consent.
Authors: Christopher Gaffney, Emily E. Vertosick, Sigrid V. Carlsson, Xin Lin, Natalie Wolchasty, Robin Hardbattle, Andrew Vickers, Behfar Ehdaie
Journal: Journal of Clinical Oncology (2023)

e17092 Background: Prostate biopsy is among the most common oncologic procedures performed annually. A substantial proportion of patients experience significant morbidity related to biopsy, including pain, anxiety, and discomfort which may discourage follow-up biopsy crucial for identifying progression or discourage enrollment in active surveillance programs that require serial biopsy. Guided meditation significantly reduces pain and anxiety during breast biopsy. We developed a brief mind-body intervention that could easily integrate into general practice for patients during prostate biopsy and compared patient-reported outcomes after biopsy with and without this intervention. Methods: We conducted a clinically-integrated randomized controlled trial (MSK IRB 18-089) of a brief mind-body intervention during prostate biopsy compared to usual care. All adult patients offered biopsy were eligible. Patients randomized to the intervention were offered both a pre-biopsy mind-body exercise and guided mindfulness meditation during biopsy via headphones. The primary outcome of interest was any severe patient-reported pain, anxiety, discomfort, or tolerability on a visual-analog scale (0-10). We compared the proportion of men in each arm reporting a severe score (7-10) on any of the four scales using Fisher’s exact test. The pre-specified clinically relevant improvement justifying integration into clinical practice was 15%. We compared means separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. Results: 238 patients (119 per arm) enrolled. 102 in the intervention arm and 94 in the usual care arm proceeded to biopsy and completed the questionnaire. A total of 37/94 (39%) and 38/102 (37%) patients in the usual care and the intervention arms, respectively, reported severe scores in any of the four domains, a difference of 2.1% (95% confidence interval -13, 17%, p = 0.8). The upper bound of the confidence interval includes the pre-specified clinically relevant difference. There was no evidence of a difference in mean post-biopsy anxiety (p = 0.3), discomfort (p = 0.09), pain (p = 0.4) or tolerability scores (p = 0.2), Table. Conclusions: There was no difference in patient reported outcomes between a mind-body intervention and usual care for prostate biopsy. Though the upper bound of the 95% confidence interval included the clinically relevant difference in severe scores, the difference in means for each outcome suggests a clinically meaningful benefit for this brief mindfulness intervention is unlikely. [Table: see text]
Treatment trends and prognostic factors related to histology of squamous cell carcinoma of the prostate: A SEER review.
Authors: Vaishnavi Siripurapu, Melisa Pasli, Arjun Bhatt, Lucas W. Ashley, Julian Gordon, Matthew Sean Peach
Journal: Journal of Clinical Oncology (2023)

e17120 Background: Excluding skin cancers, prostate cancer is the most common malignancy in males. Over 93% of prostate cancers are adenocarcinomas, and as such, an abundance of literature exists with regards to its screening, treatment, and prognosis. Often overlooked, however, data is lacking with regards to squamous cell carcinoma (SCC) of the prostate, a rare alternative form of prostatic cancer comprising fewer than 1% of malignancies. Given the rarity of SCC of the prostate there are neither accepted treatment guidelines nor consistent characterizations of the disease’s histogenesis and histopathology. This study seeks to improve existing guidelines on the treatment of prostate SCC by supplementing current literature with a novel method of longitudinal data collection in the form of the SEER database. Methods: This was a retrospective cohort study utilizing the Surveillance, Epidemiology and End Results (SEER) database sponsored by the National Cancer Institute (NCI). Investigated variables entailed patient demographics such as race and age, tumor characteristics including grade, tumor type, and histopathologic characteristics. Treatment modalities (surgical resection, radiation therapy, and systemic therapy) as well as disease characteristics were considered in generating Kaplan Meier overall survival (OS) curves compared using log rank test. Results: The most abundantly utilized treatment was surgery (58.6%), either alone or in conjunction with systemic and radiotherapy. Surgery alone was utilized for 24 patients and chemotherapy alone was utilized for 7 patients. Interestingly, only 14% of patients received multimodality treatment. Prostatic squamous cell carcinoma was the ultimate cause of death in 63.8% of cases. Kaplan Meier analysis demonstrated a median OS of 13 months. When stratifying by histopathologic characteristics, our results showed a significant difference in overall survival between patients with papillary carcinoma, with the median survival time of four years, and non-keratinizing squamous cell carcinoma, with a median survival time of one year (p = 0.005). Conclusions: Further studies are warranted regarding this exceedingly rare and understudied malignancy. The current analysis suggests subclassification of SSC of the prostate into papillary versus non-keratinizing squamous cell carcinoma may yield valuable prognostic information. Further research may emphasize this distinction as well as the role of multimodal treatment which appears to be underrepresented in SSC of the prostate when compared to other similar malignancies.
Neoadjuvant immunotherapy in hepatocellular carcinoma: A systematic review and meta-analysis.
Authors: Jay Parekh, Soniya Abraham, Haripriya Andanamala, Asad Rehman, Yiyu Xie, Yaw Adjepong, Stacey Stein
Journal: Journal of Clinical Oncology (2023)

e16232 Background: The addition of immunotherapy in neoadjuvant hepatocellular carcinoma (HCC) has been studied recently in early phase clinical trials due to high rate of recurrence after surgery. We aim to systematically review the evidence of efficacy and safety of neoadjuvant immunotherapy treatment. Methods: We carried out a systematic search on MEDLINE, Cochrane, and ASCO meetings library. Screening was done to include clinical trials with HCC patients who underwent any combination of neoadjuvant immune checkpoint inhibitors (ICIs). Quality assessment was performed using methodological index for non-randomized studies (MINORS) tool. The primary efficacy outcomes evaluated included complete pathological response (pCR), major pathological response (MPR), 1 year recurrence free survival (RFS) and overall response rate (ORR). Treatment related adverse events (TRAE) were assessed as a safety outcome. Predefined subgroup analysis was performed based on studies including of tyrosine kinase inhibitors (TKIs) in regimen. Data was analyzed using R version 4.2.1. Results: 5 phase I/II clinical trials were included consisting of 96 patients. Trials administered neoadjuvant immunotherapy agents nivolumab (with TKI cabozantinib) (N = 1), camrelizumab (with TKI apatinib) (N = 1), cemiplimab (N = 1) and nivolumab plus ipilimumab (N = 2). 78(81.2%) of patients were males. 56(59.3%) of patients had viral etiology. 14(14.5%) patients had surgeries delayed or cancelled due to any cause per trial protocols. Meta-analysis of 96 patients from 5 trials showed a pooled pCR rate of 14.49% (95% CI: 6.82 to 23.93%) with low heterogeneity (I 2 = 0%, p value 0.55). Pooling the MPR resulted in an estimate of 35.30% (95% CI: 18.80% to 53.57%) with significant heterogeneity (I 2 = 58.8%, p value 0.04). Three trials with total 45 patients reported a 12-month RFS rate of 51.08% (95% CI: 40.59 to 70.67%) with significant heterogeneity (I 2 = 84.2%, p value 0.002). The overall response rate was 13.7% (95% CI: 6.9 to 22.1%) (I2 =0%, p =0.8). Overall rate of TRAE of any grade was 73.8% (95% CI: 63.1 to 82.5%) (I2 = 83.4%, p &lt;0.001) among all trials and grade 3 adverse events was 21.21% (95% CI: 11.4 to 32.7%) (I2 = 33.8%, p = 0.159). 17(17.8%) patients had elevation in liver enzymes. On subgroup analyses, no difference in pathological outcomes, ORR and grade 3 adverse events was observed with addition of TKIs. Exploratory analysis showed no difference in pCR rates with single ICI vs combination with ipilimumab. Conclusions: The addition of ICIs in neoadjuvant settings appears to be a safe and feasible option. The addition of TKIs to neoadjuvant ICIs does not appear to affect pathological and safety outcomes. Further studies are needed to identify ICI based regimens to improve pCR rates and validate pathological outcomes in HCC after correlating with recurrence and survival.
Correlation of low B7-H6 expression with efficacy of immunotherapy inpatients with melanoma.
Authors: Jian Chen, Deqin Li, Weiwei Zhang, Shujie Song, Dengjun Sun, Ningning Luo, Huan Yi, Yingxue Qi, Mengmeng Li, Tingting Sun, Chuang Qi
Journal: Journal of Clinical Oncology (2023)

e21556 Background: B7-H6 (NCR3LG1) can bind to NKp30 to trigger antitumor NK cell activation and cytokine secretion. Our previous studies have shown that in gastric cancer, B7-H6 high expression was associated with better prognosis and the low expression of B7-H6 group was correlated with better immune microenvironment. However, the effect of B7-H6 expression on immunotherapy is unknown. Herein, we used the data from a clinically annotated cohort of melanoma patients treated with ICI to analyze the influence of B7-H6 expression on immunotherapy. Methods: The gene expression profile, gene mutation information and clinical data were extracted from the supplementary data in melanoma cohort (PMID: 31792460). Maximally selected rank statistics was used to select the optimum threshold for B7-H6 expression, and the patients was divided into two groups according to the expression of B7-H6, high group and low group. Kaplan-Meier survival analysis was used to evaluate the influence of B7-H6 expression on OS prognosis. Associations between variables and OS survival were tested using univariate and multivariate Cox and displayed by forest (R package). Results: We selected 3.14 as the optimum threshold of B7-H6 expression, and the patients was divided into high group (B7-H6 expression＞3.14) and low group (B7-H6 expression≤3.14). The results showed that low group was significantly associated with longer overall survival (p value = 0.048) in cohort of melanoma patients treated with anti-PD1 ICI, which was consistent with our previous results that low expression of B7-H6 group was correlated with better immune microenvironment. We selected primary lesion type, TMB and the expression of B7-H6 factors for univariate and multivariate analysis. TMB-H (top 25%) (p value = 0.051) and B7-H6 (p value = 0.051) low expression were associated with a better OS. Then the patients were divided into four groups according to the TMB and B7-H6 expression and analyzed the difference in the four groups. The results showed that in patients with TMB-L, B7-H6 low group had significant better OS than the B7-H6 high group (p value = 0.032). Conclusions: The low B7-H6 expression was correlated with better efficacy immunotherapy. The effect of B7-H6 expression on immunotherapy needs to be further prospective trial validation.
In situ immune impact of nivolumab + ipilimumab combination before standard chemoradiation therapy (RTCT) for FIGO IB3-IVA in patients (pts) with cervical squamous carcinoma: COLIBRI trial, a GINECO study.
Authors: Isabelle Laure Ray-Coquard, Marie-Christine Kaminsky-Forrett, Ryotaro Ohkuma, Aymeric De Montfort, Florence Joly, Isabelle Treilleux, Sarah Ghamry-Barrin, Diana Bello-Roufai, Pierre Saintigny, Antoine Angelergues, Lucas Michon, Anne-Claire Hardy-Bessard, Alexandra Lainé, Aude-Marie Savoye, Justine Berthet, Christophe Caux, Fabrice Lecuru, Bertrand Dubois, Sarah Lagarde Bétrian
Journal: Journal of Clinical Oncology (2023)

5501 Background: We report the results of a window-of-opportunity phase 2 trial using neoadjuvant nivolumab + ipilimumab followed by standard chemoradiation therapy (RTCT) in cervical squamous cell carcinoma pts using the CD8 + /FOXP3 + ratio as a surrogate marker of immune checkpoint blockade (ICB) in situ effect. Association with better clinical outcome after neoadjuvant chemotherapy and higher CD8 + /FOXP3 + ratio was described in cervical cancer pts. However, immune modulation after ICB and correlation with treatment response needs to be characterized. Methods: The primary objective was to explore the changes in the ratio of CD8 + /FOXP3 + in tumor biopsies performed before and after ICB (prior to standard RTCT) by multiplex-immunofluorescence (mIF) analyzing densities of CD8 effector T cells (CD8 + : CD3 + CD8 + FOXP3 - ) and CD4 regulatory T cells (FOXP3 + : CD3 + CD8 - FOXP3 + ). To normalize the distribution of the values, mIF data were log-transformed (log10). Targeted gene expression profiling of 2,549 genes using HTG technology allowed us to evaluate the 27-gene based ‘HOT’ score reported to be associated with immunologically active tumors (Foy J-P. et al., 2022, Eur J Can). Results: Pts received 1 cycle of nivolumab 3 mg/kg (D1D15) + ipilimumab 1 mg/kg (D1) before starting RTCT + brachytherapy. After RTCT, pts could continue nivolumab in maintenance 480 mg total dose every 28 days for 6 months. Forty pts were treated (including 50% FIGO III-IV). There were no new or unexpected toxicity. Grade≥3 AEs related to ICB occurred in 3 pts. mIF data of the 28 evaluable pts revealed an increase of total CD8 + cells (Wilcoxon, p=0.009), proliferating CD8 + cells (p=0.002) and CD8 + /FOXP3 + ratio (p=0.03) between baseline and before RTCT. In the 37 pts evaluable by HTG, a significant increase of expression of the CD8A gene (paired t-test, p=2.2e-05) and the ‘HOT’ score (paired t-test, p=3.1e-06) was observed after ICB. The Objective Response Rate on primary tumor before, after, at the end of treatment (EOT) is reported in table. Correlation between CD8 + /FOXP3 + ratio, the ‘HOT’ score and response to treatment will be presented. Conclusions: These data indicate that neoadjuvant nivolumab + ipilimumab is safe and orchestrates de novo immune responses in cervical squamous cell carcinoma. The 82.5% CR rate on primary tumor 6 months post RTCT suggests favorable clinical outcomes. Clinical trial information: NCT04256213 . [Table: see text]